Chlorambucil derivatives have been previously described in U.S. Pat. No. 5,602,278 (“the '278 patent”), which is incorporated herein in its entirety by reference thereto. The '278 patent describes the use of chlorambucil and N-oxide derivates thereof in hypoxic environments, and more particularly chlorambuci in combination with hydralazine to create such reactive conditions. However, the complexity of tumor condition and the value of N-oxides derivatives in treating a range of diseases associated with hypoxia-inducible factor was not appreciated by the '278 patent.
A number of people have studied the N-oxide derivative of chlorambucil to determine whether this agent would provide selective toxicity to hypoxic tumor cells. Some studies have reported that the N-oxide of chlorambucil are ineffective as anti-tumor agents because this derivative is not preferentially toxic under hypoxia. Others reported that the N-oxide of chlorambucil showed no enhancement of hypoxic selectivity beyond the value for chlorambucil. However, the '278 patent demonstrated that chlorambucil and its rearranged product was effective when administered with hydralazine to thereby create a hypoxic environment.
This invention relates to pharmaceutical formulations containing compounds of the present invention. The formulation may also comprise one or more of such compounds together with one or more of a pharmaceutically acceptable carrier, a diluent, an aqueous solution, an adjuvant, or another compound useful in treating various medical conditions.
This invention also includes a method of medical treatment comprising the use of such compounds. The method may also comprise using such compounds together with other methods of medical treatment.